What is the Role of Tropomyosin in Zebrafish Development
A long protein strand composed of two fully alpha helical chains in a coiled-coil dimmer, and binds along the length of the actin filament. It is also bound to bead-like protein complex (troponin) in which, together, they regulate the actin-myosin interactions in muscle contraction. (biology online)
The tropomyosin, together with troponin, acts like a “molecular switch” that controls the interaction of actin and myosin. In the absence of a nerve impulse, the tropomyosin lies fittingly on the groove of the actin filament, blocking the myosin-binding sites in actin. At this point the muscle is said to be relaxed or at rest. In the presence of nerve impulse, a cascade of reactions occurs that causes the release of calcium ions (from the sarcoplasmic reticulum). The calcium then binds to troponin, which causes a shift in the position of tropomyosin-troponin on theactin filament, unblocking the myosin-binding sites. This allows the myosin heads to bind with actin molecules, resulting in muscle shortening and contraction. Soon, the calcium levels become low again that the troponin-tropomyosin shifts back, blocking the myosin-binding sites again. (biology online)
Tropomyosins are rod like coiled coil dimers that form continuous polymers along the major groove of most actin filaments. In striated muscle, tropomyosin regulates the actin-myosin interaction and, hence, contraction of muscle. Tropomyosin also contributes to most, if not all, functions of the actin cytoskeleton, and its role is essential for the viability of a wide range of organisms. The ability of tropomyosin to contribute to the many functions of the actin cytoskeleton is related to the temporal and spatial regulation of expression of tropomyosin isoforms. Qualitative and quantitative changes in tropomyosin isoform expression accompany morphogenesis in a range of cell types. The isoforms are segregated to different intracellular pools of actin filaments and confer different properties to these filaments. Mutations in tropomyosins are directly involved in cardiac and skeletal muscle diseases. Alterations in tropomyosin expression directly contribute to the growth and spread of cancer. The functional specificity of tropomyosins is related to the collaborative interactions of the isoforms with different actin binding proteins such as cofilin, gelsolin, Arp 2/3, myosin, caldesmon, and tropomodulin. (Gunning et al)
Actin is a globular protein which is polymerized into filamentous actin (F-actin). The mechanism of actin polymerization is known to be important in cell motility, changes in cell morphology, cell division and intracellular movements. α-Thrombin induced a change in the cell morphology of IIC9 fibroblasts from a semi round to an elongated form, accompanied by an increase in stress fibers. Incubation of the cells with phospholipase D (PLD) from Streptomyces chromofuscus and exogenous phosphatidic acid (PA) caused similar morphological changes, whereas platelet-derived growth factor (PDGF) and phorbol 12-myristate 13-acetate (PMA) induced different changes, e.g., disruption of stress fibers and cell rounding. α-Thrombin, PDGF, and exogenous PLD increased PA by 20-40%, and PMA produced a smaller increase. α-Thrombin and exogenous PLD produced rapid increases in the amount of filamentous actin (F-actin) that were sustained for at least 60 min. However, PDGF produced a transient increase of F-actin at 1 min and PMA caused no significant change. Dioctanoylglycerol was ineffective except at 50 μg/ml. Phospholipase C from Bacillus cereus, which increased diacylglycerol (DAG) but not PA, did not change F-actin content. Down-regulation of protein kinase C (PKC) did not block actin polymerization induced by α-thrombin. H-7 was also ineffective. Exogenous PA activated actin polymerization with a significant effect at 0.01 μg/ml and a maximal increase at 1 μg/ml. No other phospholipids tested, including polyphosphoinositides, significantly activated actin polymerization. PDGF partially inhibited PA-induced actin polymerization after an initial increase at 1 min. PMA completely or largely blocked actin polymerization induced by PA or PLD. These results show that PC-derived PA, but not DAG or PKC, activates actin polymerization in IIC9 fibroblasts, and indicate that PDGF and PMA have inhibitory effects on PA-induced actin polymerization. (Exton, John H. and Ha, Kwon-Soo)
Among the model systems for studying development, the zebrafish has become prized because its transparent embryo develops outside the mother’s body. The zebrafish has helped biologists identify many genes involved in embryogenesis and, because it’s a vertebrate animal, has become a valuable resource for identifying genes involved in human disease. (Patterson) Zebrafish are cheaper to maintain than rodents, produce large numbers of transparent eggs, and some zebrafish assays could be scaled-up into medium and high throughput screens. However, advances in automation and imaging are required. Zebrafish cannot replace mammalian models in the drug development pipeline. Nevertheless, they can provide a cost-effective bridge between cell-based assays and mammalian whole-organism models. (Brittijn et al)
Reference:
Brittijn, Sebastiaan A.; Belmamoune, Mounia; Duivesteijn, Suzanne; et al. Zebrafish development and regeneration: new tools for biomedical research. The International journal of developmental biology. Vol 53, Isue: 5-6; 835-850. Retrieved 10 May, 2011 from http://www.mendeley.com/research/zebrafish-development-and-regeneration-new-tools-for-biomedical-research/
Exton, John H. and Ha, Kwon-Soo. Activation of Actin Polymerization by Phosphatidic Acid Derived from Phosphatidylcholine IIC9 Fibroblasts. The Journal of Cell Biology. Vol. 123, No. 6, December 1993. Retrieved 10 May, 2011 from http://www.jstor.org/pss/1616129
Gunning, Peter; Hardeman, Edna; O’neill, Geraldine. Tropomyosin-Based Regulation of the Actin Cytoskeleton in Time and Space. Physiological Reviews. January 2008 vol. 88 no. 1 1-35. Retrieved 10 May, 2011 from http://physrev.physiology.org/content/88/1/1.full
Patterson, Mark. Zebrafish model human development and disease. 11 May, 2004. Retrieved 10 May, 2011 from http://www.eurekalert.org/pub_releases/2004-05/plos-zmh050404.php
Tropomyosin. Biology online. Retrieved 10 May, 2011 from http://www.biology-online.org/dictionary/Tropomyosin
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